{"title":"Efficient N-Trifluoromethylation of Amines with Carbon Disulfide and Silver Fluoride as Reagents","authors":"Haixia Song, Qin Wang, Xiaoying Wang, Yinbin Zhang, Xin-Hua Duan, Mingyou Hu","doi":"10.31635/ccschem.024.202404432","DOIUrl":null,"url":null,"abstract":"<p>The installation of a trifluoromethyl group onto a nitrogen atom can effectively modulate the basicity of amines owing to the strong electron-withdrawing effect of fluorine. Nevertheless, efficient and operationally simple methods for <i>N</i>-trifluoromethylation of amines are yet to be developed. This protocol involves the use of readily available secondary amines as starting materials, along with CS<sub>2</sub> and AgF as the <i>N</i>-trifluoromethylation reagents, enabling the target molecules to be synthesized in a single step. The versatility of our method was demonstrated by successfully synthesizing <i>N,N</i>-dialkyl and <i>N</i>-(hetero)aromatic <i>N</i>-CF<sub>3</sub>-containing compounds with various substituents. Moreover, this methodology has been successfully applied to the late-stage modification of complex bioactive molecules, facilitating the synthesis of <i>N</i>-CF<sub>3</sub> drug bioisosteres and <i>N</i>-CF<sub>3</sub>-tailored amino acids, which would broadly stimulate the drug discovery of <i>N</i>-CF<sub>3</sub> containing molecules.</p>","PeriodicalId":9810,"journal":{"name":"CCS Chemistry","volume":null,"pages":null},"PeriodicalIF":9.4000,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CCS Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31635/ccschem.024.202404432","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
The installation of a trifluoromethyl group onto a nitrogen atom can effectively modulate the basicity of amines owing to the strong electron-withdrawing effect of fluorine. Nevertheless, efficient and operationally simple methods for N-trifluoromethylation of amines are yet to be developed. This protocol involves the use of readily available secondary amines as starting materials, along with CS2 and AgF as the N-trifluoromethylation reagents, enabling the target molecules to be synthesized in a single step. The versatility of our method was demonstrated by successfully synthesizing N,N-dialkyl and N-(hetero)aromatic N-CF3-containing compounds with various substituents. Moreover, this methodology has been successfully applied to the late-stage modification of complex bioactive molecules, facilitating the synthesis of N-CF3 drug bioisosteres and N-CF3-tailored amino acids, which would broadly stimulate the drug discovery of N-CF3 containing molecules.
期刊介绍:
CCS Chemistry, the flagship publication of the Chinese Chemical Society, stands as a leading international chemistry journal based in China. With a commitment to global outreach in both contributions and readership, the journal operates on a fully Open Access model, eliminating subscription fees for contributing authors. Issued monthly, all articles are published online promptly upon reaching final publishable form. Additionally, authors have the option to expedite the posting process through Immediate Online Accepted Article posting, making a PDF of their accepted article available online upon journal acceptance.